PROJECT SUMMARY/ABSTRACT One of the most exciting recent advances in clinical neuroscience has been the establishment of a connection between sleep and Alzheimer's Disease and Related Dementias (ADRD). Patients with ADRD frequently experience poor sleep quality/disorders and growing evidence, including from our team, suggest that poor sleep quality increase risk of developing ADRD. This bidirectional association has profound implications for prevention and treatment, however many questions remain. Mexican Americans (MAs) represent the fastest growing ethnic group in the U.S. and MAs face numerous health disparities including greater metabolic/vascular risk compared to Non-Hispanic Whites (NHWs). Recent evidence, while controversial, suggests greater subjective sleep problems in Hispanics, but these data are lacking in older Hispanics, especially MAs, and little is known about objectively measured sleep. Our cost-efficient and innovative study will address many of these gaps. The overall objective of this proposal is to determine the association between sleep quality (objective and subjective measures) and cognitive impairment including ADRD among MAs and NHWs, and to elucidate targeted pathways linking these conditions. We will leverage the ongoing Health & Aging Brain among Latino Elders (HABLE) study to cost-efficiently investigate objectively measured sleep among 500 community-dwelling MAs and 500 NHWs across level of cognitive impairment (approximately 40% with Mild Cognitive Impairment/ADRD). The HABLE study has deep phenotyping and biomarkers for metabolic/vascular health. In addition, all participants will have a brain MRI and a subset will have amyloid PET scans, cost-efficiently enabling our investigation of neurodegenerative and vascular/inflammatory pathways associated with sleep quality. We propose to conduct these aims as part of the HABLE-Dormir ancillary study: 1) To characterize objective and subjective sleep quality among older NHWs and MAs across the cognitive spectrum, 2) To examine the longitudinal association between sleep quality and 2 to 3-year cognitive decline, 3) To determine the association between sleep quality and key mechanistic pathways including vascular and inflammation and 4) To investigate the association between sleep quality and biomarkers of amyloid (PET scans and plasma A?40 and A?42) and other measures of neurodegeneration (plasma tau, NFL, and hippocampal atrophy). We have an unprecedented opportunity, working with a very experienced and multidisciplinary team, to conduct the first-ever comprehensive investigation of several key pathways among MAs and NHWs that may link sleep and ADRD. Understanding the longitudinal association and mechanisms between sleep and ADRD among older MAs will help with the early detection and prevention of ADRD in this underserved population as well as all older adults.